Document Detail


Modulation of NSAID-induced antinociceptive and anti-inflammatory effects by alpha2-adrenoceptor agonists with gastroprotective effects.
MedLine Citation:
PMID:  12269398     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tizanidine, an alpha2-adrenergic receptor agonist with myospasmolytic action, is indicated for the treatment of back pain either as monotherapy or in combination with nonsteridal anti-inflammatory drugs (NSAIDs). Tizanidine (0.25-1.0 mg/kg) significantly produced analgesic and anti-inflammatory effect in acetic acid induced writhing in mice and carrageenan-induced paw edema in rats, respectively. The effects were comparable with clonidine (0.25 and 0.50 mg/kg), another alpha2-agonist. Yohimbine (1 mg/kg), alpha2-adrenergic antagonist reversed the effect of tizanidine. Tizanidine (0.25 mg/kg) and clonidine (0.25 mg/kg) significantly potentiated the antinociceptive and anti-inflammatory effect of NSAIDs (nimesulide, meloxicam and naproxen). Tizanidine (1 mg/kg) did not alter basal pH, acidity (free and total) of gastric content and did not produce any mucosal injury in fasted rats. Tizanidine (1 mg/kg) significantly reduced meloxicam (UD50 3.21 mg/kg), nimesulide (UD50 24.52 mg/kg) and naproxen (UD50 14.10 mg/kg)-induced ulcerogenic effect (ulcer index, pH and free/total acidity). It is expected that tizanidine exerted gastrotprotection through stimulation of gastric and central alpha2-adrenergic receptors. Present investigation suggested that tizanidine not only enhance the analgesic and anti-inflammatory effect of NSAIDs but also improved gatstrointestinal tolerability of NSAIDs through modulation of central alpha-2-receptors. From this study, it can be speculated that tizanidine and NSAID combination therapy would prove to be a novel approach to treat nociceptive/inflammatory conditions with improved gastric tolerability of NSAIDs.
Authors:
Naveen K Jain; Shrinivas K Kulkarni; Amarjit Singh
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  70     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-09-24     Completed Date:  2002-10-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2857-69     Citation Subset:  IM    
Affiliation:
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Agonists / therapeutic use*
Animals
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
Clonidine / analogs & derivatives*,  therapeutic use
Drug Synergism
Drug Therapy, Combination
Mice
Naproxen / therapeutic use
Pain / drug therapy*
Rats
Rats, Wistar
Receptors, Adrenergic, alpha-2 / metabolism*
Stomach Ulcer / prevention & control*
Sulfonamides / therapeutic use
Thiazines / therapeutic use
Thiazoles / therapeutic use
Yohimbine / therapeutic use
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Receptors, Adrenergic, alpha-2; 0/Sulfonamides; 0/Thiazines; 0/Thiazoles; 146-48-5/Yohimbine; 22204-53-1/Naproxen; 4205-90-7/Clonidine; 51322-75-9/tizanidine; 51803-78-2/nimesulide; 71125-38-7/meloxicam

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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